Phase 1 Study of ACE-083 in Healthy Subjects

NCT02257489 | Completed Phase 1 Results

• 1 other identifier: A083-01
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and tolerability of single and multiple doses of ACE-083 as a local injection into selected skeletal muscles of healthy subjects. The study will also determine the amount of ACE-083 that reaches the systemic circulation following local administration. Additionally, the study will assess whether local administration into skeletal muscle results in an increase in the size and/or strength of the injected muscle.

Conditions

Musculoskeletal Diseases

Outcome Measures

Primary Outcomes (1)

• ACE-083 Safety and Tolerability: Number of Subjects With Adverse Events

  Safety/tolerability assessment, following intramuscular administration, includes adverse events, injection site reactions, laboratory measurements, vital signs, etc.

  From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)

Secondary Outcomes (3)

• ACE-083 Pharmacokinetics: Maximum Measured Plasma Concentrations

  PK samples were collected predose, and at 3 hours and 6 hours postdose.

• ACE-083 Pharmacodynamics

  From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)

• ACE-083 Pharmacokinetics: Time of the Maximum Measured Plasma Concentration

  PK samples were collected predose, and at 3 hours and 6 hours postdose.

Study Arms (7)

50 mg single dose

EXPERIMENTAL

8 subjects in total; 6 subjects to received ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly

Drug: ACE-083

100 mg single dose

EXPERIMENTAL

8 subjects in total; 6 subjects to received ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly

Drug: ACE-083

200 mg single dose

EXPERIMENTAL

8 subjects in total; 6 subjects to received ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly

Drug: ACE-083

100 mg multiple dose

EXPERIMENTAL

8 subjects in total; 6 subjects to received ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly

Drug: ACE-083

200 mg multiple dose

EXPERIMENTAL

8 subjects in total; 6 subjects to received ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly

Drug: ACE-083

100 mg (multiple dose)

EXPERIMENTAL

9 subjects in total; 6 subjects to received ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly

Drug: ACE-083

150 mg multiple dose

EXPERIMENTAL

9 subjects in total; 6 subjects to received ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly

Drug: ACE-083

Interventions

ACE-083 DRUG

recombinant fusion protein

100 mg (multiple dose); 100 mg multiple dose; 100 mg single dose; 150 mg multiple dose; 200 mg multiple dose; 200 mg single dose; 50 mg single dose

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women, defined by follicle stimulating hormone (FSH) level \> 40 IU/L and either 12 months of spontaneous amenorrhea or at least 6 months post-surgical bilateral oophorectomy and/or hysterectomy
• BMI 18.5-32 kg/m2
• Clinical laboratory values that meet the following criteria prior to dosing on Study Day 1: (i) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 x upper limit of normal (ULN), (ii) Calculated creatinine clearance ≥ 60 mL/min, (iii) Platelet count ≥ 100 x109/L
• Able to adhere to the study visit schedule, understand and comply with protocol requirements
• Understand and sign written informed consent

You may not qualify if:

• History of hepatitis B (HBsAg and HB core Ab), human immunodeficiency virus (HIV) antibody or active hepatitis C
• Positive drug or alcohol screen test at screening or on Day 1
• History of drug or alcohol abuse (as defined by the Investigator) or required treatment for drug or alcohol use within 2 years of Day 1
• Donation or loss ≥ 500 mL of whole blood within 2 months prior to Day 1
• History of opportunistic infection (e.g., invasive candidiasis or pneumocystis pneumonia) within 6 months prior to screening; serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to screening
• History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins
• History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
• History of clinically significant (as determined by the Investigator) cardiac, endocrine, hematologic, hepatic, immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or other disease
• Treatment with systemic glucocorticoid therapy, statin medication, insulin, oral hormone replacement therapy or any other therapy (including investigational) with known or intended effects on muscle within 3 months prior to Day 1
• Treatment with anti-platelet, anti-coagulant, or any other therapy (including investigational) with known or intended effects on bleeding risk within 1 week prior to Day 1
• Treatment with another investigational drug, or approved therapy for investigational use within 4 weeks prior to Day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to Day 1, whichever is longer
• Treatment within 3 months prior to Day 1 with any potent cytochrome P450 (CYP) 3A4/5 inhibitors (e.g., verapamil, ketoconazole, micronazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, delavirdine) or CYP3A4/5 inducers (carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, St. John's wort)
• Subject is unwilling or unable to maintain physical activity at baseline level for the duration of the study
• Subject has any condition that would prevent MRI scanning (e.g., pacemaker, knee/hip replacement, metallic implant, or extreme claustrophobia)
• Subject is unsuitable for enrollment in the opinion of the Investigator or Sponsor for other unspecified reasons

Sponsors & Collaborators

• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: lead

Study Sites (1)

Acceleron Investigative Site

Lincoln, Nebraska, 68502, United States

Location

Related Publications (1)

• Glasser CE, Gartner MR, Wilson D, Miller B, Sherman ML, Attie KM. Locally acting ACE-083 increases muscle volume in healthy volunteers. Muscle Nerve. 2018 Jun;57(6):921-926. doi: 10.1002/mus.26113. Epub 2018 Mar 15.

  PMID: 29486514 DERIVED

MeSH Terms

Conditions

Musculoskeletal Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Clinical Trials Manager

  Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2014
• First Posted: October 6, 2014
• Study Start: September 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: April 1, 2016
• Last Updated: September 23, 2022
• Results First Posted: July 8, 2019

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)